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https://www.readbyqxmd.com/read/28433630/loss-of-murc-cavin-4-induces-jnk-and-mmp-9-activity-enhancement-in-vascular-smooth-muscle-cells-and-exacerbates-abdominal-aortic-aneurysm
#1
Kotaro Miyagawa, Takehiro Ogata, Tomomi Ueyama, Takeru Kasahara, Naohiko Nakanishi, Daisuke Naito, Takuya Taniguchi, Tetsuro Hamaoka, Naoki Maruyama, Masahiro Nishi, Taizo Kimura, Hiroyuki Yamada, Hiroki Aoki, Satoaki Matoba
Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC(-/-)) mice subjected to periaortic application of CaCl2 developed AAAs...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28433076/identification-of-ntrk3-fusions-in-childhood-melanocytic-neoplasms
#2
Lu Wang, Klaus J Busam, Ryma Benayed, Robert Cimera, Jiajing Wang, Ryan Denley, Mamta Rao, Ruth Aryeequaye, Kerry Mullaney, Long Cao, Marc Ladanyi, Meera Hameed
Spitzoid neoplasms are a distinct group of melanocytic tumors. Genetically, they lack mutations in common melanoma-associated oncogenes. Recent studies have shown that spitzoid tumors may contain a variety of kinase fusions, including ROS1, NTRK1, ALK, BRAF, and RET fusions. We report herein the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or atypical features, based on genome-wide copy number analysis by single-nucleotide polymorphism array, which showed intragenic copy number changes in NTRK3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28432706/varied-pathological-and-therapeutic-response-effects-associated-with-chchd2-mutant-and-risk-variants
#3
Murni Tio, Rujing Wen, Yih Lin Lim, Zul Haikhel Bin Zukifli, Shaoping Xie, Patrick Ho, Zhidong Zhou, Tong-Wey Koh, Yi Zhao, Eng-King Tan
Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) have been associated with late-onset Parkinson disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking. Utilizing transgenic Drosophila model, we examined the relative pathophysiologic effect of the pathogenic (c.182C>T, p.Thr61Ile and c.434G>A, p.Arg145Gln) and the risk (c.5C>T, p.Pro2Leu) CHCHD2 variants. All the transgenic models exhibited locomotor dysfunction which could be exacerbated by rotenone exposure, dopaminergic neuron degeneration, reduction in lifespan, mitochondrial dysfunction, oxidative stress and impairment in synaptic transmission...
April 21, 2017: Human Mutation
https://www.readbyqxmd.com/read/28431148/truncated-orf1-proteins-can-suppress-line-1-retrotransposition-in-trans
#4
Mark Sokolowski, May Chynces, Dawn deHaro, Claiborne M Christian, Victoria P Belancio
Long interspersed element 1 (L1) is an autonomous non-LTR retroelement that is active in mammalian genomes. Although retrotranspositionally incompetent and functional L1 loci are present in the same genomes, it remains unknown whether non-functional L1s have any trans effect on mobilization of active elements. Using bioinformatic analysis, we identified over a thousand of human L1 loci containing at least one stop codon in their ORF1 sequence. RNAseq analysis confirmed that many of these loci are expressed...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28430966/decreased-thromboembolic-stroke-but-not-atherosclerosis-or-vascular-remodeling-in-mice-with-rock2-deficient-platelets
#5
Nikola Sladojevic, Goo Taeg Oh, Hyung-Hwan Kim, Lea M Beaulieu, Hervé Falet, Karol Kaminski, Jane E Freedman, James K Liao
Aims: Rho-associated coiled-coil containing kinase (ROCK)-2 is an important mediator of the actin cytoskeleton. Because changes in the actin cytoskeleton are critical for platelet function, we hypothesized that ROCK2 in platelets will play important role in thrombosis and can be potentially a target for therapeutic intervention in thromboembolic stroke. Methods and Results: We generated platelet-specific ROCK2-deficient mice (ROCK2 Plt-/- ) from conditional ROCK2 fl°x/fl°x and platelet factor (PF)-4-Cre transgenic mice...
April 14, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28422092/hierarchical-assembly-of-centriole-subdistal-appendages-via-centrosome-binding-proteins-ccdc120-and-ccdc68
#6
Ning Huang, Yuqing Xia, Donghui Zhang, Song Wang, Yitian Bao, Runsheng He, Junlin Teng, Jianguo Chen
In animal cells, the centrosome is the main microtubule-organizing centre where microtubules are nucleated and anchored. The centriole subdistal appendages (SDAs) are the key structures that anchor microtubules in interphase cells, but the composition and assembly mechanisms of SDAs are not well understood. Here, we reveal that centrosome-binding proteins, coiled-coil domain containing (CCDC) 120 and CCDC68 are two novel SDA components required for hierarchical SDA assembly in human cells. CCDC120 is anchored to SDAs by ODF2 and recruits CEP170 and Ninein to the centrosome through different coiled-coil domains at its N terminus...
April 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28417161/ift54-regulates-ift20-stability-but-is-not-essential-for-tubulin-transport-during-ciliogenesis
#7
Xin Zhu, Yinwen Liang, Feng Gao, Junmin Pan
Intraflagellar transport (IFT) is required for ciliogenesis by ferrying ciliary components using IFT complexes as cargo adaptors. IFT54 is a component of the IFT-B complex and is also associated with cytoplasmic microtubules (MTs). Loss of IFT54 impairs cilia assembly as well as cytoplasmic MT dynamics. The N-terminal calponin homology (CH) domain of IFT54 interacts with tubulins/MTs and has been proposed to transport tubulin during ciliogenesis, whereas the C-terminal coiled-coil (CC) domain binds IFT20. However, the precise function of these domains in vivo is not well understood...
April 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28413047/a-homolog-of-teleostean-signal-transducer-and-activator-of-transcription-3-stat3-from-rock-bream-oplegnathus-fasciatus-structural-insights-transcriptional-modulation-and-subcellular-localization
#8
S D N K Bathige, William Shanthakumar Thulasitha, Navaneethaiyer Umasuthan, J D H E Jayasinghe, Qiang Wan, Bo-Hye Nam, Jehee Lee
Signal transducer and activator of transcription 3 (STAT3) is one of the crucial transcription factors in the Janus kinase (JAK)/STAT signaling pathway, and it was previously considered as acute phase response factor. A number of interleukins (ILs) such as IL-5, IL-6, IL-9, IL-10, IL-12, and IL-22 are known to be involved in activation of STAT3. In addition, various growth factors and pathogenic or oxidative stresses mediate the activation of a wide range of functions via STAT3. In this study, a STAT3 homolog was identified and functionally characterized from rock bream (RbSTAT3), Oplegnathus fasciatus...
April 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28412885/antenatal-taurine-supplementation-in-fetal-rats-with-growth-restriction-improves-neural-stem-cell-proliferation-by-inhibiting-the-activities-of-rho-family-factors
#9
Yan Wang, Xiang-Wen Li, Jing Liu, Wei Fu
OBJECTIVE: To investigate whether antenatal taurine supplementation improves neural stem cell proliferation in rats with fetal growth restriction (FGR) through regulating the activity of Rho family factors. METHODS: FGR models were established via food restriction throughout pregnancy. Pregnant rats were randomly divided into the control group, the FGR group (given 40% of the normal daily feeding in the control group), and the Taurine group (FGR model treated with 300 mg/kg·d taurine from gestational day seven)...
April 16, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28410370/a-systematic-screen-for-morphological-abnormalities-during-fission-yeast-sexual-reproduction-identifies-a-mechanism-of-actin-aster-formation-for-cell-fusion
#10
Omaya Dudin, Laura Merlini, Felipe O Bendezú, Raphaël Groux, Vincent Vincenzetti, Sophie G Martin
In non-motile fungi, sexual reproduction relies on strong morphogenetic changes in response to pheromone signaling. We report here on a systematic screen for morphological abnormalities of the mating process in fission yeast Schizosaccharomyces pombe. We derived a homothallic (self-fertile) collection of viable deletions, which, upon visual screening, revealed a plethora of phenotypes affecting all stages of the mating process, including cell polarization, cell fusion and sporulation. Cell fusion relies on the formation of the fusion focus, an aster-like F-actin structure that is marked by strong local accumulation of the myosin V Myo52, which concentrates secretion at the fusion site...
April 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28406021/nup62-coiled-coil-motif-provides-plasticity-for-triple-helix-bundle-formation
#11
Pravin S Dewangan, Parshuram J Sonawane, Ankita Rai Chouksey, Radha Chauhan
The central transport channel of vertebrate nuclear pore complex (NPCs) is made up of nucleoporins: Nup62, Nup54 and Nup58. The coiled-coil domains in α-helical regions of these nucleoporins are thought to be crucial for several protein-protein interactions in the NPC sub-complexes. In this study, we determined the crystal structure of the coiled-coil domain of rat Nup62 fragment (362-425) to 2.4 Å resolution. The crystal structure shows conserved coiled-coil domain as a parallel three helix bundle for the Nup62(362-425) fragment...
April 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/28402887/the-closed-state-of-the-thin-filament-is-not-occupied-in-fully-activated-skeletal-muscle
#12
Sergey Y Bershitsky, Natalia A Koubassova, Michael A Ferenczi, Galina V Kopylova, Theyencheri Narayanan, Andrey K Tsaturyan
Muscle contraction is powered by actin-myosin interaction controlled by Ca(2+) via the regulatory proteins troponin (Tn) and tropomyosin (Tpm), which are associated with actin filaments. Tpm forms coiled-coil dimers, which assemble into a helical strand that runs along the whole ∼1 μm length of a thin filament. In the absence of Ca(2+), Tn that is tightly bound to Tpm binds actin and holds the Tpm strand in the blocked, or B, state, where Tpm shields actin from the binding of myosin heads. Ca(2+) binding to Tn releases the Tpm from actin so that it moves azimuthally around the filament axis to a closed, or C, state, where actin is partially available for weak binding of myosin heads...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28402881/stability-and-conformation-of-a-chemoreceptor-hamp-domain-chimera-correlates-with-signaling-properties
#13
Nattakan Sukomon, Joanne Widom, Peter P Borbat, Jack H Freed, Brian R Crane
HAMP domains are dimeric, four-helix bundles that transduce conformational signals in bacterial receptors. Genetic studies of the Escherichia coli serine receptor (Tsr) provide an opportunity to understand HAMP conformational behavior in terms of functional output. To increase its stability, the Tsr HAMP domain was spliced into a poly-HAMP unit from the Pseudomonas aeruginosa Aer2 receptor. Within the chimera, the Tsr HAMP undergoes a thermal melting transition at a temperature much lower than that of the Aer2 HAMP domains...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28395329/vitamin-d-suppresses-oxidative-stress-induced-microparticle-release-by-human-umbilical-vein-endothelial-cells
#14
Xiuyue Jia, Jie Xu, Yang Gu, Xin Gu, Weimin Li, Yuping Wang
Endothelial microparticle (MP) release was increased in numerous cardiovascular diseases including preeclampsia. Oxidative stress is a potent inducer of endothelial dysfunction. In this study, we aimed to investigate if vitamin D could protect endothelial cells (ECs) from MP release induced by oxidative stress. Endothelial cell (from human umbilical vein) oxidative stress was induced by cultivation of cells under lowered oxygen condition (2%O2) for 48 h and cells cultured under standard condition (21%O2) served as control...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28394926/gp73-represses-host-innate-immune-response-to-promote-virus-replication-by-facilitating-mavs-and-traf6-degradation
#15
Xuewu Zhang, Chengliang Zhu, Tianci Wang, Hui Jiang, Yahui Ren, Qi Zhang, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients' serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28392072/non-nuclear-pool-of-splicing-factor-sfpq-regulates-axonal-transcripts-required-for-normal-motor-development
#16
Swapna Thomas-Jinu, Patricia M Gordon, Triona Fielding, Richard Taylor, Bradley N Smith, Victoria Snowden, Eric Blanc, Caroline Vance, Simon Topp, Chun-Hao Wong, Holger Bielen, Katherine L Williams, Emily P McCann, Garth A Nicholson, Alejandro Pan-Vazquez, Archa H Fox, Charles S Bond, William S Talbot, Ian P Blair, Christopher E Shaw, Corinne Houart
Recent progress revealed the complexity of RNA processing and its association to human disorders. Here, we unveil a new facet of this complexity. Complete loss of function of the ubiquitous splicing factor SFPQ affects zebrafish motoneuron differentiation cell autonomously. In addition to its nuclear localization, the protein unexpectedly localizes to motor axons. The cytosolic version of SFPQ abolishes motor axonal defects, rescuing key transcripts, and restores motility in the paralyzed sfpq null mutants, indicating a non-nuclear processing role in motor axons...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28391065/novel-lipoproteoplex-delivers-keap1-sirna-based-gene-therapy-to-accelerate-diabetic-wound-healing
#17
Piul S Rabbani, Anna Zhou, Zachary M Borab, Joseph A Frezzo, Nikita Srivastava, Haresh T More, William J Rifkin, Joshua A David, Samuel J Berens, Raymond Chen, Sophia Hameedi, Muhammad H Junejo, Camille Kim, Rita A Sartor, Che F Liu, Pierre B Saadeh, Jin K Montclare, Daniel J Ceradini
Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC)...
April 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28389563/structure-of-the-wipa-protein-reveals-a-novel-tyrosine-protein-phosphatase-effector-from-legionella-pneumophila
#18
Nikos Pinotsis, Gabriel Waksman
Legionnaires disease is a severe form of pneumonia caused by the bacterium Legionella pneumophila. L. pneumophila pathogenicity relies on secretion of more than 300 effector proteins by a type IVb secretion system. Among these Legionella effectors, WipA has been primarily studied because of its dependence on a chaperone complex, IcmSW, for translocation through the secretion system, but its role in pathogenicity has remained unknown. In this study, we present the crystal structure of a large fragment of WipA, WipA435...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28387769/-99-tc-m-octreotide-scintigraphy-and-serum-eye-muscle-antibodies-in-evaluation-of-active-thyroid-associated-ophthalmopathy
#19
B Sun, Z Zhang, C Dong, Y Zhang, C Yan, S Li
PurposeAs an autoimmune inflammatory disorder, active thyroid-associated ophthalmopathy (TAO) is managed optimally by immunosuppression. In this study, we aimed to evaluate octreotide scintigraphy and the level of serum extraocular muscle antibodies in TAO activity.Patients and methodsThis prospective study comprised 304 patients with active TAO (the clinical activity score; CAS≥3), 73 with inactive TAO (CAS<3), 128 with Graves' disease (GD) without ophthalmopathy, and 100 healthy subjects. Moderate-to-severe active TAO patients (CAS≥5) received intravenous injection of methylprednisolone; mild active patients (3≤CAS≤4) received periocular injection of triamcinolone acetonide...
April 7, 2017: Eye
https://www.readbyqxmd.com/read/28384393/d-cysteine-ligands-control-metal-geometries-within-de-novo-designed-three-stranded-coiled-coils
#20
Vincent Louis Pecoraro, Leela Ruckthong, Anna F A Peacock, Cherilyn E Pascoe, Lars Hemmingsen, Jeanne A Stuckey
While metal ion binding to naturally occurring L-amino acid proteins is well documented, understanding the impact of the opposite chirality (D) amino acids on the structure and stereochemistry of metals is in its infancy. We examine the effect of a D-configuration cysteine within a designed L-amino acid three-stranded coiled coil in order to enforce a precise coordination number on a metal center. The D-chirality does not alter the native fold, but the side-chain reorientation modifies the sterics of the metal binding pocket...
April 6, 2017: Chemistry: a European Journal
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